Cisplatin is a highly effective and extensively used anticancer drug. Higher doses of cisplatinmanifest acute nephrotoxicity and this is one of the limiting factors of this drug in cancerchemotherapy. The effect of the oyster mushroom extract to ameliorate cisplatin ( cis platinum (II)diammine dichloride) induced nephrotoxicity and restoration of antioxidant defence system in micewas investigated. The investigations showed that prior administration of methanolic extract ofPleurotus florida at a dose of 500 and 1000mg/Kg body weight significantly reduced elevatedserum creatinine and urea levels and increased superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GPx) activities in the kidney, consequent to cisplatin treatment, in a dosedependent manner. The extract restored the decreased reduced glutathione (GSH) activity andincreased malondialdehyde (MDA) level due to cisplatin administration. The results thusindicated that oyster mushroom extract rendered significant protection against cisplatin inducednephrotoxicity and depletion of antioxidant defence system in a dose dependent manner. Sinceoyster mushrooms are excellently edible and non-toxic, the finding reported here is of significantuse in cancer chemotherapy.